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Monday, August 6, 2007

What is the best design? Continuation on antidepressants

Continued treatment for 6 to 12 months beyond the acute phase of depression reduces the risk of relapse to 50%. Patients taking antidepressants during the continuation phase are at least 50% less likely to experience a relapse compared to patients with placebo. These continuation studies of antidepressants have used two different designs:

1. Patients are initially treated with an antidepressant, responders are then randomised to continue with the antidepressant or switched to placebo in a double-blind matter, both doctor and patient don't know what they are on.

2. Patients are treated with an antidepressant or placebo in a double blind fashion, responders to active treatment and placebo are continued on the treatment to which they initially responded.

The authors of this study in the Journal of Clinical Psychopharmacology hypothesised that the design of the study would impact on the likelyhood of relapse (getting a depression again). They speculated that the first design would result in more relapse since there is an obvious change in treatment, patients can be aware that they initially received active medication, and there is now a change that they will will be switched to placebo. Expectation of a positive outcome in this design would be lower.
The authors conducted a meta-analysis of antidepressant continuation studies and compared the relapse rates using these 2 different designs. They identified 16 continuation studies of new-generation antidepressants, 11 using the first design and 5 using the second design.
In the second design the frequency of relapse was lower compared to the studies using the first design. Also the difference between relapse with the antidepressant and placebo was greater with this design.
The design of these studies has a significant impact on the absolute percentage of patients who relapse on both active medication and placebo, as well as an effect on the difference between relapse frequency between antidepressant and placebo.
Other factors such as longer continuation phase, demographic factors, depression severity, broader definition of treatment response during the acute phase, and a broader definition of relapse did not explain the outcome of this meta-analysis. Drug withdrawal did not account for the difference in absolute relapse rates related to study design.

Treatment optimism for patients and raters may explain reduced relapse rates in the second design. Design should be taken into accoun when comparing results of continuation studies.

Impact of Study Design on the Results of Continuation Studies of Antidepressants.
Brief Reports

Journal of Clinical Psychopharmacology. 27(2):177-181, April 2007.
Zimmerman, Mark MD; Posternak, Michael A. MD; Ruggero, Camilo J. PhD

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